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Male obesity is associated with subfertility and increased disease risk of offspring.It is unknown if effects can be reversed through pharmacological interventions.Five-to 6-week-old C57BL6 male mice were fed control diet (n =10,CD) or high-fat diet (n =20,HFD) for 16 weeks.Animals fed with a HFD were then allocated to continuation of HFD (n =8) or HFD with metformin 28 mg kg-1 day-1 (n =8) for 6 weeks.Animals fed with CD continued on a CD (n =9).Males were mated with fertile C57BL6 females for the assessment of pregnancy and fetal growth.Sperm motility,spermatozoa and testicular morphology,sperm-zona pellucida binding,sperm reactive oxygen species (ROS) (intracellular[DCFDA],superoxide[MSR],and oxidative DNA lesions[80HdG]),and mitochondrial membrane potential (JC1) were assessed.Mefformin treatment of HFD males improved glucose tolerance (+12％,P ＜ 0.05) and reduced Homeostatic Model Assessment of Insulin Resistance (HOMA-IR;-36％,P ＜ 0.05).This occurred in the absence of a change in body weight or adiposity.Mefformin treatment of HFD-fed males restored testicular morphology (+33％,P＜0.05),sperm motility (+66％,P＜ 0.05),sperm-zona pellucida binding (+25％,P＜ 0.05),sperm intracellular ROS concentrations (-32％,P ＜ 0.05),and oxidative DNA lesions (-45％,P ＜ 0.05) to the levels of the CD males.Metformin treatment of HFD fathers increased fetal weights and lengths compared with those born to HFD fathers (+8％,P ＜ 0.05),with fetal lengths restored to those of fetuses of CD males.Short-term mefformin treatment in men who are obese could be a potential intervention for the treatment of subfertility,without the need for a reduction in body weight/adiposity.