Changes in skeletal muscle adiponectin induction have been described in obesity and exercise. However, whether changes are consistent across muscle types and with different exercise modalities, remain unclear. This study compared the effects of diet and two isocaloric training programs on adiponectin induction and its regulators in three muscles: quadriceps (exercising/glycolytic-oxidative), gastrocnemius (exercising/glycolytic), and masseter (nonexercising/glycolytic). Ten-week-old male C57BL/6 mice were fed a high-fat diet (HFD) (45% fat) or standard CHOW diet (12% fat) ad libitum and underwent one of two training regimes: (1) constant-moderate training (END), or (2) high intensity interval training (HIIT) for 10 weeks (3 x 40 min sessions/week). Chow and HFD-fed untrained mice were used as control. Compared with Chow, HFD induced an increase in protein levels of low-molecular weight (LMW) adiponectin in gastrocnemius and masseter (similar to 2-fold; P < 0.05), and a decrease of high-molecular weight adiponectin (HMW-most bioactive form) in quadriceps (similar to 0.5-fold; P < 0.05). Only END prevented these changes (P < 0.05). HFD induced a decrease of adiponectin receptor 1 (AdipoR1) protein in exercising muscles of untrained mice (similar to 0.5-0.8-fold; P < 0.05); notably, END also decreased AdipoR1 protein levels in lean and HFD mice. This type of training also normalized HFD-driven mRNA changes found in some adiponectin downstream factors (sirtuin 1, Pgc-1a, and Ucp2) in the three muscles tested. Our results indicate that diet, muscle type/activity, and exercise modality influences muscle adiponectin profile, and some of its mediators. These parameters should be taken into consideration when investigating this endocrine response of the skeletal muscle, particularly in the context of obesity and metabolic disorders.