Caseous lymphadenitis has been globally a prevalent disease among farmed small ruminants for over a century. As its chronic disease, sex hormone profiles and cellular changes of reproductive organs in infections associated with Corynebacterium pseudotuberculosisis and its exotoxin phospholipase D have been very few or absent. This study was conducted to acquire a better way of understanding the reproductive pathophysiology response of Corynebacterium pseudotuberculosisis and its exotoxin in mouse model. In this study, 64 healthy mice, 2-3 weeks of old, were divided equally into 3 groups, where the first group of mice were interperitoneally inoculated with 1.0 ml of sterile phosphate buffer solution (PBS), pH 7, the second group of mice were interperitoneally inoculated with 1.0 ml of 10 colony forming unit (CFU) of live C. pseudotuberculosis and the third group of mice were interperitoneally inoculated with 1.0 ml of single dose of exotoxin (PLD) extracted from C. pseudotuberculosis. Following infection, clinical signs were observed and blood samples were collected by cardiac puncture for sex hormone analysis. For microscopic examinations, the mice were euthanized using cervical dislocation approach and the reproductive organs were collected. The results revealed that there was no significant differences (p<0.05) in the concentration of estrogen and progesterone levels between whole cell and exotoxin groups. Concentration of progesterone in PLD treated group (15.37 ± 2.32 pg/ml) was lower than control group (17.61 ± 2.91pg/ml). The concentration of testosterone in C. pseudotuberculosis (2.98 ± 3.70 pg/ml) was significantly (p<0.05) different from both control group (16.58 ± 3.67 pg/ml) and PLD (11.84 ± 3.19 pg/ml). Microscopically, cellular changes were observed in organs included ovaries, uterus, testicles and epididymis. In C. pseudotuberculosis infected group, infiltration of polymorph nuclear leukocytes with congestion, degeneration and necrosis were documented in almost all investigated parameters. For exotoxin PLD infected group, the observed cellular changes included severe hemorrhage, thrombus formation, degeneration, vacuolation and necrosis. Therefore, the results of this study indicated that there were significant differences in sex hormones and cellular changes of reproductive organs associated with infection Corynebacterium pseudotuberculosisis and its exotoxin phospholipase D (PLD).