The current study was carried out to evaluate the effect of vitamin C on ceftriaxone induced adverse effects in rats. Twenty-four adult male albino rats were randomly divided into 3 equal groups. Group(I) received 1ml saline orally once daily for 14 days. Group(II) received 1ml saline orally once daily for 7 days followed by a 7-once day-treatment with ceftriaxone intra-peritoneally(180 mg/kg b. wt.). Group(III) received vitamin C orally(100 mg/kg b. wt.) once daily for 7 days , followed by a 7-once day treatment with both oral vitamin C and intraperitoneal ceftriaxone. At the end of the experiment, half of animals were sacrificed under light ether anesthesia on 1st day post-treatment and the other half on 7th day post-treatment. Blood samples were collected for biochemical analysis. Livers and kidneys were collected for histo-pathological examination. Biochemical analysis revealed a significant increase in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase(AST), urea, creatinine and malondialdehyde (MDA). with a significant decrease in catalase(CAT) and superoxide dismutase (SOD) activities in ceftriaxone treated group. Group(III) showed a significant decrease in serum levels of ALT, AST, urea, creatinine and MDA, with a significant increase in CAT and SOD activities. Histopathological examination of liver and kidney of rats in group(II) showed severe hepatocellular necrosis, macrosteatosis, portal fibrosis, portal inflammatory cells infiltrations, necrotic renal tubules and glomerular changes. An improvement of histopathological pictures of liver and kidney was recorded in group(III). This study concluded that vitamin C ameliorates the biochemical and histopathological changes associated with ceftriaxone treatment in rats.