Studies are conflicting to whether low volume resistance training (RT) is as effective as high-volume RT protocols with respect to promoting morphological and molecular adaptations. Thus, the aim of the present study was to compare, using a climbing a vertical ladder, the effects of 8 weeks, 3 times per week, resistance training with 4 sets (RT4), resistance training with 8 sets (RT8) and without resistance training control (CON) on gastrocnemius muscle proteome using liquid chromatography mass spectrometry (LC-MS/MS) and cross sectional area (CSA) of rats. Fifty-two proteins were identified by LC-MS/MS, with 39 in common between the three groups, two in common between RT8 and CON, one in common between RT8 and RT4, four exclusive in the CON, one in the RT8, and four in the RT4. The RT8 group had a reduced abundance of 12 proteins, mostly involved in muscle protein synthesis, carbohydrate metabolism, tricarboxylic acid cycle, anti-oxidant defense, and oxygen transport. Otherwise one protein involved with energy transduction as compared with CON group showed high abundance. There was no qualitative protein abundance difference between RT4 and CON groups. These results revealed that high volume RT induced undesirable disturbances on skeletal muscle proteins, while lower volume RT resulted in similar gains in skeletal muscle hypertrophy without impairment of proteome. The CSA was significantly higher in RT8 group when compared to RT4 group, which was significantly higher than CON group. However, no differences were found between trained groups when the gastrocnemius CSA were normalized by the total body weight.