Dietary proteins have been reported to be beneficial for lipid metabolism, tissue growth, development, and repair, as well as immune response. The interactions of dietary proteins and their digested products may regulate the physiology and metabolism of the gastrointestinal tract. However, proteins are largely digested before reaching the large intestine. The present study investigated the use of the non-dietary protein, silk sericin, in rats. Rats were fed either with casein or sericin proteins. Their body weight, food consumption, and complete blood count were measured. The results showed that during the experimental periods, rats fed with casein and sericin diets had no significant changes on body weight, food consumption, or complete blood count. Sericin-fed rats had a significantly decreased CD8a and CD80 positive cells when compared with standard casein protein.In conclusion, dietary proteins may have a differential impact on the leukocyte profile. The mechanisms underlying these changes are not clear but they might be due to the different amino acid compositions of the proteins studied.