Introduction Resistance training may be carried out via different methods that have been shown to have differing effects on muscle metabolism and signalling pathways. As a matter of fact a resistance training program is a composite of several important variables including that may affect physiological outcomes. On the other way also an high intensity interval exercise performed on cycloergometer has been demonstrated to influence some metabolic pathway as PGC-1α. Thus, the aim of our study was to analyse mRNA response to a single bout of high-intensity resistance training (HIRT), traditional resistance training (TRT) and high-intensity interval training (HIT). Methods 12 healthy subjects performed in two different moments and with different legs HIRT and TRT protocol. HIRT consisted in 2 sets of 6/2/2 reps with incomplete rest between (20″) sets while TRT consisted of 4 sets x15 reps with 1’15” of rest between sets. HIT was performed on a cycloergometer as follow: 30″ of all out with 4′ of rest, repeated for 4 times. Biopsies from the vastus lateralis were taken one week before training sessions (pre), immediately after (T0), 6 hours after (T6) and 24 hours after (T24) training. The following genes, related to hypertrophy, metabolism, autophagy and inflammation, was analysed by RT-qPCR: IGF-1, IGF-14a, MGF, myostatin, STARS, PGC-1α, PGC-1α-4, Atrogin, Beclin, IL6, myogenin Results Our data showed that HIRT seems to influence in a greater extent the gene linked to mechanical deformation (MGF) and STARS, whilst TRT seems influence STARS and IGF-1. HIT influenced IGF-14a, Beclin, IL6, myogenin, PGC-1α and myostatin. Discussion Our results suggest that different kind of exercise may influence different early genes after exercise. An high resistance training (HIRT) affects mechanical-related factors whilst a more traditional, long duration resistance training (TRT) seems to influence the IGF-1 pathway. The HIT exercise increases in a significant manner PGC-1α but also muscle atrophy related genes as atrogin, beclin and myostatin.