Abstract: The present study was carried out to assess and compare the effects of Valproic Acid (VPA) and Trichostatin A (TSA) on in vitro development of sheep Somatic Cell Nuclear Transfer (SCNT) embryos. The results showed that treatment of cloned sheep embryos with 4 mM VPA or 50 nM TSA for 24 h after activation could significantly improve blastocyst rate compared to the control (30.7 vs. 23.3 vs. 16.7%, respectively p<0.05). VPA treatment resulted in a significant higher blastocyst rate than that of TSA-treated group (p<0.05). Moreover, VPA treatment significantly increased (p<0.05) total cell number per blastocyst compared with the TSA treatment and control groups (78.8±9.3 vs. 69.6±9.7 vs. 64.1±8.6, respectively). Furthermore, VPA treatment increased expression of the development-related genes OCT4 and SOX2 in SCNT blastocysts. These results demonstrate that VPA may be more potent than TSA in supporting developmental competence of cloned embryos.