Excess adiposity increases systemic inflammation, which is implicated in various diseases. Physical activity, both forced and voluntary, may reverse the disease risk associated with weight gain from high-fat, high-calorie feeding. Purpose. To determine if 8-weeks of aerobic exercise training combined with low-fat feeding reverses changes in disease risk, monocyte concentration and monocyte TLR2/TLR4 expression. Methods. For 12-months, 24 CD-1 mice underwent a pre-treatment phase, consuming either a low-fat (10% kcal from fat, N=6) or high-fat (60% kcal from fat, N=18) diet ad libitum. High-fat fed mice were randomly assigned to one of three groups (N=6/group): V-EX (high-fat pre-treatment, switched to low-fat chow, free access to running wheel 5 days/week), F-EX (high-fat pre-treatment, switched to low-fat chow, forced treadmill running at 22 m-min-1, 60-min/day, 5 days/week), or SD (high-fat pre-treatment, switched to low-fat chow, no exercise). Mice that were pre-treated with the low fat diet were used as a control group (CN, N=6). Outcome measurements were made on weekly saphenous vein blood samples using 3-color flow cytometry. Blood glucose and cholesterol concentration were analyzed weekly using a commercially available glucose and cholesterol monitoring system. IPGTT was performed at baseline and week 8 and analyzed as area under the curve. Results. All groups lost significant body weight over 8-weeks (P<0.001). V-EX lost 36.4% and F-EX lost 27.1% from baseline to week 8 (P<0.001). V-EX ran 4.4x times more than F-EX (P<0.001). There were no significant effects for blood cholesterol. CN had 26% higher glucose levels than V-EX (P=0.009). On average, there was a 59.3% decrease in IPGTT AUC from baseline to week 8 and V-EX decreased 37.4% more than CN. At week 8, monocyte concentration was 6x higher than week 1 (P=0.002). Specifically, V-EX was greater than both CN (48.9%) and F-EX (58.9%). Cell-surface TLR2 expression was significantly greater at week 6 (54.6%) and week 8 (22.9%) relative to baseline measurements. Monocyte cell-surface TLR4 expression increased over the course of the intervention, such that week 8 was greater than baseline (P<0.001). Similar to TLR2, there was no significant group effect for TLR4 expression. Conclusions. Consumption of a low-fat diet and exercise caused significantly more weight loss than low-fat diet alone. Overall, there were decreases in insulin resistance in all groups and decreased fasting blood glucose, suggesting there may have been a decrease in disease risk factors. Increases in monocyte concentration and TLR2/4 cell-surface expression suggest that it may be the diet and exercise intervention was not long enough to elicit changes in inflammation following such a long period of high-fat feeding. More research is needed to understand these changes. This study was useful in understanding the overall changes that occurred with a diet and exercise intervention. It was also an important step in directly comparing forced and voluntary exercise.