Aim: Diabetes can be associated with a number of peripheral neuropathies, which include painful diabetic neuropathy and cardiovascular autonomic neuropathy. Therefore, patients with diabetes may have complicated cardiovascular responses to noxious stimulation. However the details are unclear. Methods: Diabetic model (DM) rats were prepared by administering streptozotocin (STZ). Three weeks after STZ, a pressure sensor and needle electrodes were implanted and connected to telemetry system for measurement of blood pressure (BP) and ECG. Four weeks after STZ, formalin test was conducted on upper lip. Pain related behavior (face-rubbing; PRB), BP, and heart rate (HR) were recorded for 60 min. Two hours after the formalin test, brain was perfused and expression of c-Fos in the caudal part of spinal trigeminal nucleus (Vc) was evaluated. Furthermore, BP and HR variability were analyzed using the MemCalc method. Control rats (no STZ treatment) were also examined. Results: There were no significant differences in the PRB and HR-HF between the DM and control rats. The elevation in BP and HR in the DM rats was smaller than that in the control rats (p 0.01). Changes in SBF-LF in the DM rats were significantly less than those in the control rats (p 0.01). Expression of c-Fos in Vc was higher in the DM rats than in the control rats (p 0.05). Discussion: Although increased expression of c-Fos in Vc reflects hyperalgesia to noxious stimulation, hemodynamic and autonomic responses were smaller in the DM rats. Response to noxious stimuli was complicated by neuropathy in DM rats. Keywords: diabetes mellitus, autonomic nerve, cardiovascular response, c-Fos, formalin test