The far reaching dissemination and toxic nature of pesticides and their elements seriously affects the aquatic surroundings, and exerts negative consequences on the related organisms. The present study was carried out to investigate the effect of malathion and neem oil individually and also in combination on the fresh water fish, Oreochromis mossambicus to elucidate the change in the different target organs like liver and kidney with reference to biochemical and histopathological studies. Median lethal concentration (LC50) of neem oil and malathion was maintained for acute toxicity (96 hours) and chronic toxicity (21 days) studies. Further the fishes were segregated into 4 groups where in each group contained 6 fishes. Group I fishes were maintained in tap water, Group II in neem oil, Group III fishes were maintained in malathion , Group IV fishes were maintained in both neem oil and malathion. The LC50 dose of neem oil and malathion was found to be 0.9 ml/L and 3.52 mg/L respectively. The results of biochemical analysis revealed that total protein and lipid increased in combination of neem oil and malathion which was comparatively more than that of the neem oil and malathion maintained individually. The total free sugar showed a decrease in combination as well as individually in acute toxicity study .However there is an increase in total free sugar as observed in chronic toxicity study. Histopathological study in acute and chronic toxicity (i) in liver, fishes exposed to neem oil showed normal hepatocellular architecture while fishes exposed to malathion only and those of malathion combined with neem oil showed hepatocellular degeneration while the latter showed the signs of recovery (ii) in kidney the neem oil exposed fishes showed normal renal architecture , malathion exposed fishes showed epithelial cell degeneration and necrosis, while those exposed to neem oil and malathion combined showed mild degeneration. This study indicated the action of neem oil which has interacted with malathion and reveals a protective influence on harmful effects of the toxicant.