PPARδ is a transcription factor regulating the expression of genes involved in oxidative metabolism, which may regulate blood cholesterols through transcription of oxidative and lipoprotein metabolism genes. To determine the association of skeletal muscle PPARδ content with blood lipids and lipoproteins before and following exercise, overweight and obese men (n = 9) and women (n = 7) were recruited; age, BMI, body fat percentage, and Vo(2max) were (means ± SE) 45 ± 2.5 yr, 31.9 ± 1.4 kg/m(-2), 41.1 ± 1.5%, and 26.0 ± 1.3 mLO(2)·kg(-1)·min(-1), respectively. Subjects performed 12 wk of endurance exercise training (3 sessions/wk, progressing to 500 kcal/session). To assess the acute exercise response, subjects performed a single exercise session on a treadmill (70% Vo(2max), 400 kcal energy expenditure) before and after training. Muscle and blood samples were obtained prior to any exercise and 24 h after each acute exercise session. Muscle was analyzed for protein content of PPARδ, PPARα, PGC-1α, AMPKα, and the oxidative and lipoprotein markers FAT/CD36, CPT I, COX-IV, LPL, F(1) ATPase, ABCAI, and LDL receptor. Blood was assessed for lipids and lipoproteins. Repeated-measures ANOVA revealed no influence of sex on measured outcomes. PPARδ, PGC-1α, FAT/CD36, and LPL content were enhanced following acute exercise, whereas PPARα, AMPKα, CPT I, and COX-IV content were enhanced only after exercise training. PPARδ content negatively correlated with total and LDL cholesterol concentrations primarily in the untrained condition (r ≤ -0.4946, P < 0.05), whereas AMPKα was positively correlated with HDL cholesterol concentrations regardless of exercise (r ≥ 0.5543, P < 0.05). Our findings demonstrate exercise-induced expression of skeletal muscle PPARs and their target proteins, and this expression is associated with improved blood lipids and lipoproteins in obese adults.