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We examined the effects of salsalate treatment on nutrient-induced OS and inflammation, ovarian androgen secretion, ovulation, and insulin sensitivity in PCOS. Eight lean insulin-sensitive women with PCOS and eight age- and body composition-matched ovulatory controls for baseline comparison participated in the study. The women with PCOS underwent a 12-wk treatment of salsalate, a nonsteroidal anti-inflammatory drug, at a dose of 3 g daily. Markers of OS and inflammation were quantified in mononuclear cells (MNC) and plasma from blood drawn fasting and 2 h after saturated fat ingestion before and after treatment. Ovarian androgen secretion was assessed from blood drawn fasting and 24, 48, and 72 h after human chorionic gonadotropin (HCG) administration before and after treatment. Ovulation was documented based on biphasic basal body temperatures and luteal range progesterone elevations. A two-step pancreatic clamp was performed pre- and posttreatment to measure basal endogenous glucose production (EGP) and the steady-state glucose disposal rate (GDR) during the euglycemic phase and markers of OS and inflammation in MNC and plasma during the hyperglycemic phase. Salsalate administration suppressed lipid- and glucose-stimulated reactive oxygen species generation, activated nuclear factor-\u03baB and circulating tumor necrosis factor-\u03b1, normalized basal androgen levels, and lowered HCG-stimulated androgen secretion without altering EGP or GDR. Four salsalate-treated subjects responded with two consecutive ovulations. 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