Coccidiosis in poultry is caused by protozoan parasites of the genus Eimeria, which is responsible for worldwide economic losses. The methanolic extract of Azadirachta indica (neem) leaves was used in vivo for its pharmacological, antioxidant, and anticoccidial properties. Four groups of mice were investigated. The first group was inoculated only with sterile saline and served as the control group. The second group was treated by oral gavage with neem extract (500 mg/kg) daily for 4 days. The third and fourth groups were infected with 10(3) sporulated oocysts of Eimeria papillata. The fourth group was also treated once daily with neem extract for 4 days. Paraffin sections from the jejunum as well as jejunal homogenate were prepared for the histopathological and biochemical investigations, respectively. The data showed that mice infected with E. papillata revealed an output of 6.5 × 10(5) ± 29,753 oocysts per gram feces on day 4 postinoculation. This output is significantly decreased to 2.7 × 10(5) ± 37,341 oocysts in neem-treated mice. Infection with E. papillata induced marked histopathological alterations in the jejunum in the form of inflammation, vacuolation of the epithelium, and destruction of some villi. Also, the neem extract greatly diminished body weight loss of infected mice. Moreover, the number of goblet cells stained with Alcian blue within the infected villi was significantly lowered (P ≤ 0.05). In addition, E. papillata enhanced lipid peroxidation and nitric oxide production in both serum and jejunum with concomitant reduction in glutathione. Neem induced marked improvements in all of the studied parameters as well as the histopathological features of the jejunum. Our study revealed that neem as a natural product has protective effects against E. papillata-induced coccidiosis.