Toxoplasmosis has zoonotic importance among human and domestic animals. It causes diseases in both man and animals through ingestion of oocysts that passed in faeces of cat or by ingestion of cysts in undercooked meat.The present study was designed to clarify the effect of Clindamycin (CLI) combined with Sulfadiazine (SD) on a murine model of acute toxoplasmosis. Albino Swiss mice were intraperitoneally infected with 10³ tachyzoites of the RH strain of Toxoplasma gondii and were per orally treated with either drug alone (SD) or (CLI) or both combined. Starting with day 1 for 14 days. Survival was monitored during 8 weeks. Residual infection was assessed by a bioassay of representative 4-week survivors and by parasite DNA detection using PCR for representative 8-week survivors. An effect of treatment was shown in all treated groups compared to untreated control mice. Among mice infected with parasite, SD and CLI at any dose combination protected more animals. However, treatment with SD plus CLI at 25 plus 25, 25 plus 50, and 50 plus 50 mg/kg/day protected 25, 37, and 81% of mice, respectively, thus demonstrating a significant synergistic effect of SD and CLI against T. gondii especially in cases of acute infection.