Despite the negative effects of silver nanoparticles, their application is growing rapidly, so this study was designed to investigate the adverse effects of nanosilver administration on histopathological changes and biochemical parameters as well as therapeutic efficacy of penicillamine. Four groups of six BALB/c mice were treated intraperitoneally with various dose of nanosilver and the LD50 was calculated. To investigate therapeutic efficacy of penicillamine, forty-two mice were assigned into equal seven groups. The animals of each group were treated intraperitoneally with LD50 of nanosilver and 50 or 200 mg/kg penicillamine concurrently, or 4 hours after nanosilver injection. Histopathological and serum biochemical analyses including total protein, albumin, total globulin, cholesterol, triglyceride, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total antioxidant capacity (TAC) and Malondialdehyde (MDA) were carried out. The LD50 was 1500 PPM. Results showed an increase in the levels of AST and ALT enzymes and the MDA in the mice receiving nanosilver while TAC concentration decreased. These alterations were statistically significant between the mice receiving nanosilver and those receiving nanosilver and 200 mg/kg penicillamine. Also, histopathological examination of the tissue sections of the the mice receiving 1500 PPM nanosilver showed hepatic and renal damage. Whereas, the biochemical parameters and tissue lesions improved in mice receiving 200 mg/kg penicillamine in comparison with the nanosilver exposed mice and it was shown that the extent of oxidative stress was decreased.