Objective To investigate the cause of formation of herniation found in adult male humanized mice and the effect of that herniation on humanized mice. Methods Construction humanized mice with the method of injection human hematopoietic stem cells into murine blastocysts. The phenotypic characteristics and pathological mechanism of herniation, the effects of herniation on behavior and physiological reaction of humanized mice were analyzed. Results2 months of age or older male humanized mice developed direct inguinal hernias. The loss of dense connective tissue may be the main reason of the inguinal hernias. The motor coordination and endurance of humanized mice decreased as compared with wild-type mice, but the reproductive system of male humanized mice have no difference from the wild-type mice. ConclusionsAdult male humanized mice suffer from inguinal hernias, the formation mechanism of which should be further researched.