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Introduction: While much has been published on the effect of different amounts of dietary carbohydrate (carb) on cardiovascular disease (CVD) risk, data on effects of different types of carb (simple, refined and unrefined) are limited.Objective: To determine the relative comparability for an isocaloric replacement of unrefined-carb (UC; e.g., brown rice and bread/pasta made from whole wheat flour), refined-carb (RC; e.g., white rice and bread/pasta made from white flour) and simple-carb (SC; e.g., sucrose and high fructose corn syrup) on serum lipid and lipoprotein profile, adipose tissue gene expression of macrophage and inflammation markers, cytokine secretion and adipocyte size, and cholesterol efflux in peripheral blood mononuclear cells (PBMC).Methods: Study subjects (men and postmenopausal women [N=11], 65±8 y, BMI 29.8±3.2 kg/m2, LDL-C ≥2.6 mmol/L) were provided with isocaloric diets (60% E total carb, 15% E protein, 25% E fat) enriched in SC, RC or UC for 4.5 weeks, with a 2-week washout period between diet phases, using a randomized, cross-over design. Body weight was maintained within +/- 2 kg. At the end of each diet phase serum lipid and lipoprotein profile was determined using standard methods. Abdominal subcutaneous adipose tissue biopsies were collected and used to assess gene expression of macrophage and inflammation markers, cytokine secretion, and cell size. PBMCs were isolated and cultured to assess cholesterol efflux.Results: Fasting serum TC (p=0.004) and LDL-C (p=0.002) concentrations were higher after subjects consumed the RC diet than after the SC and UC diet phases. No significant differences were observed among diets in serum HDL-C (p=0.32), VLDL-C (p=0.17), TG (p=0.19), and NEFA (p=0.99) concentrations. Adipocyte size was largest after subjects consumed the RC diet and smallest after the SC diet (p<0.0001). There were no significant differences among diets in gene expression of the macrophage markers CD14 (p=0.62) and CD68 (p=0.62), and the inflammatory markers adiponectin (p=0.66), leptin (p=0.42), and IL-6 (p=0.92), except for a trend towards higher serum amyloid-1 expression after the RC diet (p=0.059). Inflammatory cytokine secretion of adiponectin (p=0.52), leptin (p=0.89), and IL-6 (p=0.07) were not significantly different among diet phases. No significant differences were observed in macrophage cholesterol efflux among diets (p=0.18).Conclusions: Consuming the RC diet resulted in higher serum TC and LDL-C concentrations, and concurrently increased abdominal subcutaneous adipocyte size. Dietary carb type had no significant effect on markers of macrophage infiltration, inflammation or cytokine secretion in adipose tissue, or macrophage cholesterol efflux. Results from this study provide mechanistic support for the epidemiologic findings that increasing consumption of RC diet is positively associated with CVD risk.