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The goal of this study was to investigate the common clinical chemistry and distribution of xanthine oxidase (XO) in selected tissues of a mouse model of menopause. Twenty four NMRI female mice were divided into three groups: normal control (NC), and ovariectomized (OVX) groups and an estrogen-treated ovariectomized (OVX+E) group which received subcutaneous injection of estradiol benzoate (2 mg/kg). After 8 weeks, blood samples were collected for determining plasma clinical chemistry. Tissue XO activity was measured spectrophotometrically based on monitoring uric acid (UA) formation. Plasma levels of total cholesterol (TC), total protein (TP), albumin (ALB), globulin (G), and calcium, and enteric XO activity increased in OVX group as compared with NC group. Hepatic XO activity in OVX group declined in comparison with NC group. E2, TP, and G levels and liver and brain XO activities increased in OVX+E group when compared with OVX group. However, TC, high density lipoprotein cholesterol, UA, and ALB levels decreased in OVX+E group compared with OVX group. The brain and heart XO activities increased in OVX+E group as compared to that of NC group. XO activity was not detected in womb, spleen and stomach of all studied groups. XO activity was not detected in muscles of NC group while OVX and OVX+E groups showed muscle XO activity. Induction of ovariectomy produced a hypoestrogenic state that coincident with an adverse alteration of plasma clinical chemistry in mice. XO activity also changed after ovariectomy and estrogen-replacement therapy with a tissue-specific manner.