Sarcopenia results in an increase in intermuscular fat (IMF) and low density muscle (LDM), which is associated with adverse health and functional consequences. Although strength training (ST) is considered an intervention of choice for the prevention and treatment of sarcopenia, little is known about its effect on IMF or LDM. Regional fat alterations resulting from exercise interventions may be influenced by adrenergic receptor (ADR) beta2 Gln27Glu and ADR alpha2b Glu¹²/Glu⁹ gene polymorphisms. To examine the influence of these polymorphisms on mid-thigh IMF, LDM and normal density muscle (NDM), we studied 46 older men and 52 older women before and after a 10-week single leg knee extension strength training (ST) program. The ST program resulted in a substantial increase in one-repetition maximum (1-RM) strength (P = 0.0001) and NDM (P = 0.0001), but no significant changes in IMF and LDM in the whole group. However, IMF was significantly reduced with ST in subjects carrying ADR beta2 Glu27 (-2.3 cm², P = 0.028), but no significant change was observed with ADR beta2 Glu27 noncarriers (+1.5 cm², P = 0.14). The decrease in IMF in those with the ADR alpha2b Glu⁹ allele was approaching significance (-1.9 cm², P = 0.066), and significantly different (-2.9 cm², P = 0.043) from a nonsignificant increase in IMF in the ADR alpha2b Glu⁹ allele noncarriers. ADR beta2 Glu27 carriers who also carried the ADR alpha2b Glu⁹ allele experienced a significant loss of IMF with ST (-3.8 ± 1.6 cm², P = 0.018). These results suggest that the response of IMF to ST is influenced by ADR beta2 Gln27Glu and ADR alpha2b Glu¹²/Glu⁹ polymorphisms.