Objectives: To investigate whether glucosamine sodium sulfate (GlcNs) can penetrate the skin and the effects of this dietary supplement on glucose metabolism in rats.Methods: GlcNs was radiolabeled with 14 C to test its ability to pass through skin. GlcNs was also orally administered to rats at different doses. Changes in body weight and blood glucose levels were subsequently measured. In addition, levels of key enzymes related to glucose metabolism (SLC2A2 (solute carrier family 2, member 2), SLC2A4 (member 4), HK1 (hexokinase 1), NOS2 (nitric oxide synthase 2), and PRKCA (protein kinase C, alpha) were analyzed in liver and kidney tissues via immunohistochemistry.Results: Radio labeled GlcNs effectively penetrated rat skin. Rats given a daily dose of 250 mg/kg GlcNs exhibited significantly lower levels of blood glucose (p<0.05) than controls. For the 125-mg/kg group, levels of PRKCA and HK1 in kidney were significantly lower (p<0.05) than controls.Conclusions: GlcNs can be administered through the skin. Oral administration of GlcNs does not affect body weight, but may influence glucose metabolism in rats. These findings are important for research concerning diabetes and its complications in patients with arthritis.