Carbon tetrachloride (CCL) is often employed in the production of chlorofluorocarbons, petroleum refining, oil and rubber processing, and laboratory applications. Oral, subcutaneous, and inhalation exposure to CCL in animal studies have been shown to be capable of leading to various types of cancer (benign and malignant, liver, breast, and adrenal gland tumors). The present study also evaluated the protective role of infliximab (INF) against the deleterious effects of CCL on the intestinal system. Twenty-four male Sprague-Dawley rats were randomly assigned into three groups, control ( = 8), CCL ( = 8), and CCL + INF ( = 8). The control group received 1 mL isotonic saline solution only via intraperitoneal (i.p.) injection. The CCL group received a single i.p. dose of 2 mL/kg CCL. The CCL + INF group received a single i.p. dose of 7 mg/kg INF followed 24 h later by a single dose of 2 mL/kg CCL. All rats were euthanized 2 days following drug administration. CCL group samples also exhibited diffuse loss of enterocytes, vascular congestion, neutrophil infiltration, an extension of the subepithelial space and significant epithelial lifting along the length of the villi with a few denuded villous tips. In addition, CCL treatment increased intestinal malondialdehyde (MDA) level and caspase-3 positivity. On the other hand, INF decreased MDA levels, caspase-3 positivity, and loss of villous. Our findings suggest that CCL appears to exert a highly deleterious effect on the intestinal mucosa. On the other hand, INF is effective in preventing this CCL-induced intestinal injury by reducing oxidative stress and apoptosis.