Intestinal Eimerian infections are considered to be one of the most highly distributed protozoan parasitic infections among farms and domestic animals, and cause huge economic losses in the field of animal farming and meat production. All recent trends to fight infectious diseases depend upon using treatment of natural origins instead of synthetic drug therapy. Berberine is a plant derived isoquinoline alkaloid with wide spectrum pharmacological and antimicrobial activities. The current study was designed to elucidate the in-vitro and in-vivo anticoccidial activities of berberine chloride against murine intestinal Eimeria papillata infection. In-vitro measurements showed that berberine could significantly reduce the viability and sporulation percent of E. papillata unsporulated oocyst. In addition, berberine showed a pronounced in-vivo anticoccidial activity as revealed by reducing the number of zygots and developing oocysts within intestinal villi by about 90% and that of schizonts and gamonts by 58% and 30% respectively. Moreover, berberine treatment of E. papillata infected mice showed a great increase in the total antioxidant capacity within jejunum tissue. Finally, the results of the study proved both in-vitro and in-vivo anticoccidial activities of berberine chloride against the murine intestinal E. papillata infection, and could effectively correct the induced disruption in the antioxidant capacity within jejunum tissue by such infection.