Abstract: Ectoparasites are distributed all over the world but occur mainly in tropical and sub-tropical countries. Ectoparasites result in a considerable amount of blood loss, disturbances in feeding, retarded growth and decreased production. Among the ectoparasiticides ivermectin is a new endectocide and diazinon is another commonly used ectoparasiticide available in Bangladesh. The present research was designed to study the comparative efficacy of ivermectin and diazinon against ectoparasites, their effects on some clinical, hematological and biochemical parameters in sheep. For this purpose 25 sheep heavily infested with ticks and lice were randomly divided into 5 equal groups, i.e. groups B, C, D, E and F. Another group of 5 sheep free from parasitic infestation were also selected and kept as uninfected control (group A) and group B was kept as infected control group. The sheep of groups C and D were treated with recommended (200 g/kg b.w.) and higher than recommended (300 g/kg b.w.) doses of ivermectin subcutaneously. The sheep of groups E and F were treated with diazinon (spray) at recommended (0.1% soln.) and higher than recommended (0.2% soln.) doses. After injection of ivermectin and spray of diazinon all four treated and two groups were kept for 28 days and clinical, hematological and biochemical parameters were investigated at 7 days intervals. The data were collected and analyzed statistically between control and treated groups by using student ‘t` test . On the basis of lice and tick count, the efficacy of ivermectin was found 100% whereas diazinon was 82-85% effective against ectoparasitic infestation in sheep. Ivermectin and diazinon increased the feeding efficiency as compared to infected control groups. No adverse effects was observed following both the dose of ivermectin and recommended dose of diazinon. In this study, the hematological parameters, i.e. TEC and Hb% were increased significantly (p<0.01) in all treated four groups to the extent of 35-70% and 10-21% respectively. On the other hand, ESR values were decreased significantly (p<0.05). No significant change was observed on SGOT and SGPT following both the doses of ivermectin injection. However, SGOT and SGPT values were significantly (p<0.01) increased to the extent of 46-90% and 25-46% within 7-14 days of diazinon spray. However, elevated values of SGOT and SGPT became almost normal within 28 day of treatment. Among the recommended and higher than recommended doses of ivermectin and diazinon, the recommended dose of both the drugs is suitable for therapeutic purpose. Among the two drugs, ivermectin was found to be the best drug against ectoparasites showing prompt and 100% efficacy.