Heat therapy has been shown to promote capillary growth in skeletal muscle and in the heart in several animal models, but the effects of this therapy on angiogenic signaling in humans in unknown. We evaluated the acute effect of lower body heating (LBH) and unilateral thigh heating (TH) on the expression of angiogenic regulators and heat shock proteins (HSPs) in healthy young individuals. Exposure to LBH (n=18) increased core temperature (Tc) from 36.9±0.1 to 37.4±0.1ºC (p<0.01) and average leg skin temperature (T_leg) from 33.1±0.1 to 39.6±0.1ºC (p<0.01), but did not alter the levels of circulating angiogenic cytokines and bone marrow-derived pro-angiogenic cells (CD34⁺CD133⁺). In skeletal muscle, the change in mRNA expression from baseline of vascular endothelial growth factor (VEGF), angiopoietin 2 (ANGPT2), chemokines CCL2 and CX3CL1, platelet factor-4 (PF4) and several members of the HSP family was higher 30 min after the intervention in the individuals exposed to LBH (n=11) as compared to the control group (n=12). LBH also reduced the expression of transcription factor FOXO1 (p=0.03). Exposure to TH (n=14) increased T_leg from 32.8±0.2 to 40.3±0.1ºC (p<0.05) but T_c remained unaltered (36.8±0.09ºC at baseline and 36.9±0.07ºC at 90 min). This protocol upregulated the expression of VEGF, ANGPT1, ANGPT2, CCL2 and HSPs in skeletal muscle but did not affect the levels of CX3CL1, FOXO-1 and PF4. These findings suggest that both LBH and TH increase the expression of factors associated with capillary growth in human skeletal muscle.