Insulin-like growth factor-1 (IGF-1) peptides exist as single chain polypeptides consisting of about 70 amino acid residues which stimulate muscle hypertrophy via PI-3K-Akt-mTOR signaling. The purpose of the present study was to investigate the effect of a resistance exercise (RE) protocol (4 sets of squat and bench press with 85 % of 1RM) at different rest intervals between sets on serum IGF-1, cortisol (CO), creatine kinase (CK) and blood lactate concentrations. Hence, ten recreationally resistance-trained men (Mean ± SD, age=20.37 ± 2.44 years, body mass= 65.6 ± 26.70 kg) volunteered as subjects that in 4 separate sessions with 48 h from each other performed a RE protocol with 60, 90 and 120 second rest period between sets. Blood samples were collected before (Pre), immediately after (Post) and 30 min after the exercise protocols (30Post). Changes in serum IGF-1 levels were not significant between protocols. However, serum IGF-1concentration was significantly increased by 3.6 and 23 percent during RT with 60 second rest between sets at Pre and 30Post. Serum CO concentrations were significantly higher in 60 and 90 second rest protocol than 120 second protocol. Changes in serum CK and blood lactate concentrations were not significant between protocols but post exercise levels significantly increased in each protocol. The data indicate that although rest period between sets in RE to failure resulted in a significant change in CO levels, it had no effect on plasma IGF-1, CK and lactate levels. However, post exercise serum IGF-1 concentrations significantly increased only at RE to failure with 60s rest between sets