The present study was carried out to evaluate the side effects of lamivudine administration and its immunological effect in male albino rats through estimating some hematological parameters, liver and kidney functions, humoral immunity and phagocytic capacity. Forty adult male albino rats were divided into 2 groups (control and treated groups) each of 20 rats. The treated group was orally administered Lamivudine for 60 days in a dose of 9 mg/kg BW once daily. In the current study, all hematological parameters were within the normal range except the packed cell volume which increased at 60 days (45.60±0.87). IgG was increased in the treated group at 15, 30, 45 and 60 days (1183.96±11.64, 1203.58±2.02, 1185±13.27and 1181.16±11.74, P<0.01, respectively), while IgM did not reveal any significant change. In treated group, there were no significant changes in serum urea and creatinine except after 15 days of drug administration the creatinine level was significantly decreased. Aspartate aminotransferase was decreased (24.00±1.94, P<0.01) after 45 days of drug administration, while alkaline phosphatase did not significantly changed. Alanine aminotransferase was decreased (26.20±1.95, 31.40±1.77, 29±3.39 and 22±1.41, P<0.01) at 15, 30, 45 and 60 days, respectively. The total protein increased at 15, 30, 45 and 60 days of drug administration in the treated group (8.64±0.12, 8.07±0.19, 8.06±0.46 and 8.60±0.22, P<0.01, respectively). Moreover, total globulins were significantly increased at 15, 30, 45 and 60 days of drug administration (4.91±0.13, 4.92±0.35, 4.31±0.26 and 4.34±0.16, respectively). The present results revealed an increase in the phagocytic percent and phagocytic index at 30 (1.12±0.09 and 79.15±3.64) and 60 days (0.93±0.08 and 77.13±4.45) of drug administration, respectively. Based on the current findings, it may be concluded that lamivudine had no serious side effects on hematology, both liver and kidney functions with a promising immunostimulant effect.