Background: The autonomic changes and cardiorespiratory changes seen in vascular disorders are suggested to be mediated reflexly by the activation of perivascular nociceptors. The role of prostaglandins, vanilloid receptor 1, 5-hydroxytryptamine type 3, and kinin receptors is well established. Aims and Objectives: This study was conducted to understand the role of N-methyl-D-aspartate (NMDA) receptor in modulating vasosensory reflex responses evoked by Mesobuthus tumulus venom. Materials and Methods: Healthy male albino rats were anesthetized with an intra-peritoneal injection of urethane (1.5 g/kg). Tracheostomy was performed to keep the airway patent. Femoral artery was cannulated proximally as well as distally to record the blood pressure (BP) and to inject the chemicals, respectively. The effect of venom on BP, heart rate (HR), respiratory rate, and minute ventilation was recorded for 60 min at every 5 min and presented as mean ± standard error of mean. Results: Intra-arterial injection of venom produced immediate hyperventilatory response (increase of 41.6%), followed by hypoventilatory response (decrease of 40.1%), and finally sustained hyperventilatory response (increase of 53%) which was observed up to 60 min. The hypertensive response started at 40 s, peaking at 5 min (increase of 48%), and remained above the initial level subsequently. The bradycardiac response began around 5 min, peaking at 25 min (decrease of 50% in HR), and remained at that level up to 60 min. In 2-amino 5-phosphonovaleric acid (NMDA receptor antagonist) pre-treated group, the venom-induced cardiovascular responses (mean arterial pressure and HR) were markedly attenuated in comparisons to the venom only group but not the respiratory responses. Conclusions: The data provide evidence for the involvement of NMDA receptors in producing the venom-induced vasosensory reflex responses modulating the cardiovascular parameters in anesthetized rats.