One of the most important features of nano drugs is higher surface ratio than volume compared to conventional drugs that helps to increase its solubility in blood. In the present study, the effects of nano magnesium oxide and magnesium oxide were studied and compared on electrocardiographic indices in dog. For this purpose, one group of dogs (5 cases) was as control and groups 2 and 3 received nano magnesium oxide at 5 and 10mg/kg, respectively and group 4 received magnesium oxide at 10mg/kg. Cardiac function including heart rate, heart rhythm and P-QRS-T waves were evaluated by electrocardiogram standard leads before and after 1, 3 and 24 hours of drug administration. The amount of magnesium, potassium, sodium and calcium were measured in serum at above noted. Electrocardiogram parameters such as cardiac axis, duration and amplitude of P wave, QRS complex duration, Q-T and P-R interval were not significantly changed. Nevertheless, T wave amplitude was significantly decreased in group 2, after 3 hours of drug administration (p<0.01). R wave amplitude was significantly increased in group 3, after 3 hours (p<0.05). Heart rate was significantly decreased in all trial groups, after 3 hours (p<0.05). Serum magnesium level was significantly increased in all trial groups after 1 hour (p<0.001). There were not any significant differences in the amount of serum potassium, sodium and calcium. So, usage of magnesium nano-oxide and magnesium oxide can induce some effects on cardiovascular system including heart rate and some of the electrocardiographic indices. The incidence of some cardiac arrhythmias by magnesium oxide is greater than nano magnesium oxide. In conclusion, it can be stated that the exit of nano particles with the smaller molecular size from the blood is occurred more quickly, and therefore its serum concentration is lower than normal form.