This study evaluates the protective effects of a lyophilized extract of the horse mushroom, Agaricus arvensis, on hematological parameters and its antioxidative role against carbon tetrachloride (CCl4)-induced oxidative stress in rats. The protective effects of the A. arvensis extract were evaluated by comparing hematological parameters, erythrocyte fragility, and components of the antioxidant defense system (e.g., reduced glutathione [GSH] level; glutathione S-transferase, catalase, glutathione peroxidase [GPx], and superoxide dismutase activities; and malondialdehyde content in erythrocytes). The 4 experimental groups included the controls (group I), CCl4-treated rats (group II), rats treated with CCl4 + 100 mg/kg A. arvensis extract (group III), and those treated with CCl4 + 500 mg/kg A. arvensis extract (group IV). Erythrocyte hemolysis in 0.6% NaCl was lower in groups I, III, and IV (at 38%, 22%, and 34%, respectively) than in group II. GSH levels in groups I, III, and IV were higher by 54%, 12%, and 11%, respectively, than that in group II. GPx enzyme activity in group II was significantly lower than the activity in groups I, III, and IV (by 138%, 70%, and 64%, respectively). In addition, administration of the A. arvensis extract resolved the dangerous effects of CCl4 on some hematological parameters such as red blood cells, hemoglobin, hematocrit, white blood cells, platelet count, plateletcrit, and red cell distribution width. We conclude that the A. arvensis extract has therapeutic effects against CCl4-induced oxidative stress, reduces erythrocyte fragility, and improves a number of hematological parameters in rats.