The search for natural biologically active substances having a neuroprotective effect against cerebral ischemia-reperfusion injury is one of the major priorities of modern neuroscience and medicine. Intranasal insulin (INI) exerts a pronounced restorative effect on various neurodegenerative diseases, but the mechanisms of its action and its therapeutic effects in cerebral ischemia have not been well studied, including in type 2 diabetes mellitus (DM2) which increases the risk of cerebrovascular dysfunction. The aim of the work was to study the effect of INI on metabolic parameters and inflammatory factors in male Wistar rats with DM2, exposed to cerebral ischemia, as compared to nondiabetic animals. DM2 was induced by a combination of high-fat diet and low-dose (25 mg/kg) streptozotocin administration. Cerebral ischemia was studied in a rat model of global forebrain ischemia-reperfusion (IR) injury induced by occlusion of both common carotid arteries, followed by a 7-day reperfusion. Two h after the end of ischemic exposure, the rats were treated with INI at a dose of 0.5 or 2.0 IU/rat, after which the drug was administered at the same dose, once a day, for the following 7 days. INI was found to prevent body weight loss in both nondiabetic and DM2 IR-exposed rats, while elevating plasma total cholesterol levels and epididymal fat fraction in IR-exposed nondiabetic animals only. In IR-exposed DM2 rats, INI (at both doses used) reduced postprandial plasma levels of glucose and insulin, indicative of improved glucose tolerance, as well as plasma levels of inflammatory factors, C-reactive protein (at a dose of 0.5 IU/rat/day), and tumor necrosis factor-α (at a dose of 2 IU/rat/day), indicative of its anti-inflammatory potential. Thus, a post-IR course treatment with INI improves metabolic parameters and abates inflammatory responses in DM2 rats, which may be in high demand when correcting ischemic stroke in patients with DM2.