Murraya koenigii (Mk) leaves possess a hypoglycemic effect. Activity of paraoxonase 1 (PON1), a HDL-associated antioxidant enzyme, was found to be decreased during hyperglycemia. The present study explored the effect of Murraya koenigii leaves (MkL) on paraoxonase 1 activity in order to control the oxidative stress in diabetes. Hyperglycemia was induced in mice by a single dose of streptozotocin (200 mg kg-1 body weight). Diabetic mice were treated with the aqueous extract of MkL orally once daily for 15 days. Doses of 75 and 150 mg kg-1 body weight of the aqueous MkL extract decreased the blood sugar level significantly in a dose dependant manner. MkL administration significantly reduced oxidative stress by decreasing the MDA level and by increasing GSH level, SOD as well as catalase activity. However, PON1 activity was found to be increased after administration of aqueous MkL extract. MkL treatment also possesses a hypolipidemic effect as inferred from the decrease in total cholesterol, triglyceride level and increase in HDL-C concentration. Here we conclude that after MkL treatment, not only the antioxidant parameters like SOD, CAT, GSH and MDA, but also PON1 may be involved in decreasing the oxidative stress associated with diabetes. © 2013 The Royal Society of Chemistry.