Background: Ischemia reperfusion (I/R) islife-threatening condition.Reperfusion following ischemia can further exacerbate damage of different tissues,especially in the presence of Diabetes mellitus (DM). Metformin (MET) an antidiabetic medication has been reported to exert an anti-inflammatoryeffect.Pentoxyfylline (PTX)used in intermittent claudication, has been reported to exert an anti-inflammatory and antioxidant effects .Ambroxol(AMB) an expectorant antitussive mucolytic drug has also demonstrated protective effects on ischemic damage. The rationale of this study is to test potential effects of PTX and AMB against remote organ injury induced by hind limb ischemia on top of STZ induced type 2 diabetes mellitus in rats and there efficacy compared with the standard hypoglycaemic drug MET. Aim of the study:The present study was designed to evaluate the potential effects of PTX and AMBon fasting blood glucose, liver function,kidney function, reduced glutathione andnuclear factor kappa B.Materials and methods: Rats were classified into: Group I: control normal. Group II: diabetic iscemic not treated (diseased group). Group III was pretreated with MET. Group IV: pretreated with PTX, Group V: pretreated with AMB,Group VI: pretreated with combination of MET with PTX, Group VII: pretreated with combination of MET with AMB.All treated groups received drugs for 7days prior to induction of hindlimb ischemia in diabetic rat. Results:All groups showed significant improvement in all parameters.Conculsion: All tested drugs alone or in combination showed improvement of parameters of IR on top of DM. It is found that all combinations show more efficacy than each drug alone.