Abstract: An experiment was conducted to determine the response of the gut associated lymphoid tissues (GALT) to very virulent IBD virus (vvIBDV) of Malaysian isolate. Twenty eight days old specific pathogen free (SPF) chickens were divided into two groups namely: the control and IBD groups. The chickens each in the IBD group were inoculated orally with vvIBDV of Malaysian isolate at a dose of 104.5EID50/ml/chicken. Clinical abnormalities were recorded and three chickens in the IBD group were sacrificed at 0, 1, 2, 3, 4, 5, 6 and 12hrs, and days 1, 2, 3, 4, and 6 post infections (pi). Three chickens each in the control group were scarified at days 0, 1, 2, 3, 4 and 6 of the trial. On necropsy, the body weight, bursa weight and gross lesions were recorded. Samples at the junction of oesophagus and proventriculus, junction of proventriculus and gizzard, Meckel`s diverticulum, middle part of ileum, caecal tonsil and bursa of Fabricius were collected and processed for histopathology. Blood was collected for detection of IBD antibody using enzyme linked immunosorbent assay (ELISA). Typical clinical signs of IBDV infections were observed in chickens from the IBD group at days 2 and 3 pi. Histopathology examination showed highly increased of lymphoid cells at the junction of oesophagus and proventriculus at 4, 5, 6 and 12 hrs, and days 1 and 2 pi, with moderate increased thereafter when compared to the control group. Marked lymphoid cells increment was also observed at the junction of proventriculus and gizzard at 6 and 12 hrs, and days 1 and 2 pi, and mild to moderate increased observed thereafter. No significant changes observed in the Meckel`s diverticulum throughout the trial. Tissues from the middle part of ileum was absent of any lymphoid aggregation in both the control and IBD groups. Moderate increased of lymphoid cells with some cells showed degeneration and necrosis occurred in the caecal tonsils at 5, 6 and 12 hrs, and days 1 and 2 pi. At days 3 and 4 pi, moderate to severe follicular degeneration and necrosis with mild congestion or haemorrhages were recorded. The bursa of Fabricius showed moderate to severe lesions at days 2, 3, 4 and 6 pi. Immunoperoxidase staining of the bursa showed intense positive reaction in the reticular epithelial lining and medulla of the bursa follicles at 4, 5, 6 and 12 hrs pi. At days 1, 2 and 3 pi, the cortex of the bursa follicle stained more intensely then the medulla. The control group was without any clinical signs, gross or microscopic lesions throughout the trial. IBD antibody titre was first detected in the IBD group at day 4 pi (552+489) and further increased at day 6 pi (1496+137). It was concluded that vvIBDV of Malaysian isolate can cause lesions in the GALT. The virus is first replicate in the GALT including in the lymphoid cells aggregation at the upper part of the gastrointestinal tract, at the junction of oesophagus and proventriculus, and junction of proventriculus and gizzard, and at the caecal tonsil leading to primary viraemia and replication of the virus in the bursa of Fabricius following oral route of vvIBDV infections. The response of GALT at the middle part of ileum could not determine due to absent of the lymphoid cells aggregation in the samples examined, whilst no significant response of the Meckel`s deverticulum to vvIBDV was recorded.