Toluene is widely used all over the world as a volatile organic compound and manufactured in big amounts for use in various applications including paints, inks, adhesives, varnishes and plastics. Aim of the work: This study was implemented to evaluate the role of buffalo milk in ameliorating toxic effects of toluene in adult male albino rats. Methodology:72 adult male albino rats were used in this study.They were divided into five groups as follow: Group I (negative control) 12 rats received regular diet and water to measure basic parameters.Group II (positive control) 24 rats subdivided into 2 equal groups: Subgroup IIa :12 rats received 1 ml of corn oil . Subgroup IIb : 12 rats received 1ml of distelled water . Group III (pasturalized buffalo milk group (PBM)12 rats received 1ml of buffalo milk .Group IV (toluene group)12 rats received toluene 900mg/kg dissolved in corn oil . Group V (toluene and pasturalized buffalo milk group) 12 rats received toluene 900mg/kg followed by 1ml of buffalo milk for 7 days. At the end of the study, blood samples were collected for estimating (serum ALP, ALT, albumin, creatinine, MDA, TAC). Then livers and kidneys were extracted for histopathological and immunohistochemistry (caspase-3) examination. Results: The result of the study revealed that administration of toluene for 7 days induced significant increase in ALP, ALT, creatinine, serum MDA and significant reduction in serum albumin and TAC. It also induced histopathological alterations in liver and kidney with increased caspase-3 immunoreactivity. Administration of PBM with toluene for 7 days improved toluene induced histopathological alterations in liver and kidney with decreased caspase-3 immunoreactivity. Also, PBM caused significantly beneficial effect on liver and kidney parameters; In addition, it decreased serum MDA level and increased serum TAC. Conclusion: Buffalo milk has partial protective effects against toluene induced hepatotoxicityand nephrotoxicity,