The objective of the current studies was to analyze the relation of sex steroid treatment with the pattern of uterine secretory proteins and production of tumor necrosis factor α(TNFα) and nitric oxide (NO) by murine macrophages. Specific pathogen free (SPF) CD1 mice were ovariectomized and divided into 6 groups which were treated with different sex steroids: progesterone (group 2), estradiole (group 3), progesterone plus estradiole (group 4), estradiole plus progesterone (group 5), testosterone (group 6) and placebo (group 1). The treatments were continued by subcutaneous embedding of hormone pellets for 30 days. Total white blood cell counts in groups 4 and 5 showed statistically higher total leukocyte count (P≦0.05) than that in groups 2 and 6 (p≦0.05). Lipopolysaccharide (LPS)-stimulated peritoneal macrophages from estrogen-treated mice produced a significantly higher of NO than those in the other groups (p≦0.05). TNFα production by the macrophages significantly increased by estrogen or testosterone treatment compared with the control (p≦0.05). LPS induced a 2 fold production of both TNFαand NO by peritoneal macrophages. It was observed that steroid treatment induced a de novo synthesis of products with patterns specific to uterine proteins. Our results showed that sex steroids affect the macrophage function and modulate the pattern of secretory uterine proteins. The usefulness of the mouse model with subcutaneous embedding of hormone was also demonstrated.