Background: The enzyme HGPRT 5-phosphoribosyl converts to hypoxanthine or guanine to build up IMP or GMP as an ATP and GTP precursor in the purine nucleotides salvage pathway. This enzymeis most active in the liver, blood cells, nervous system, and skeletal muscles. In fact, the normal activity of this enzyme is involved in the salvage of 90% of free nucleotides and thereby contributes to the economy of purine in cells. Minor decrease or defect of this enzyme results in the increased xanthine, uric acid, and oxygen free radicals. Reports suggest the relationship between this enzyme and the level of physical preparation, antioxidant capacity, and low blood uric acid levels in active individuals. However, the effect of different types of exercise, especially high-intensity intermittent exercise on this enzyme is not clear. Objectives: The present study aimed to investigate the possible compatibility of this enzyme and some purine nucleotide cycle variables in a short-term high-intensity interval training. Methods: 18 healthy, untrained, male, eligible volunteers (based on their age, height, and weight) were randomly divided into control and training groups. The training group rode the bicycle ergometer with maximum intensity for 2 weeks (3 sessions per week) with 45-second repetitions and a 4-minute rest between the sets. Blood samples were collected for measuring HGPRT, hypoxanthine, xanthine, and uric acid before and 48 hours after the last training session, and data were analyzed using analysis of covariance at alpha level of 0.05. Results: A significant increase was found in the levels of hypoxanthine (P = 0.001) and xanthine (P = 0.001) while a statistically significant reduction was found in the level of uric acid (P = 0.02). However, after training, the HGPRT serum level did not increase significantly (P = 0.386). Conclusions: The results suggest that this short-term program was able to improve the variables involved in the purine nucleotide recycling pathway,