This study has developed to evaluate the protecting effect of Quercetin in phenylhydrazine (PHZ) induced hemolytic anemia comparing to traditional used antioxidant (Silymarin). For that 45 male white Albino rats were randomly allocated into 5 groups, control group, phenylhydrazine group (PHZ) which injected by PHZ (20 mg/kg b.w, I/P at day 7th, 8th and 9th), Quercetin+PHZ group (Quercetin, 50 mg/kg b.w per os every day for 16 days), silymarin+PHZ group (Silymarin, 100 mg/kg b.w per os every day for 16 days) and Quercetin group. Serum samples of these groups were collected after 3, 5 and 10 days after injection of PHZ and used for biochemical and oxidative stress analysis. Also, specimens from spleen were collected for histopathologial examination. The results of this study showed that, Quercetin ameliorated phenylhydrazine effect on total protein, total bilirubin, direct and indirect bilirubin, LDH, iron and ferritin levels. Also, Quercetin improved levels of oxidative stress parameters GSH, SOD and MDA, and had protective effect on tissue of spleen. Therefore, Quercetin had protective effect in experimental phenylhydrazine-induced hemolytic anemia. Also it was more potent antioxidant than Silymarin.