Adipose tissue has a central role in the maintenance of whole-body energy homeostasis. In healthy individuals, adipose tissue releases adipokines, which contribute to maintenance of insulin sensitivity and lipid and glucose metabolism as well as the regulation of satiety and inflammation. Obesity disrupts adipocyte metabolism, which leads to chronic systemic inflammation and metabolic dysfunction (MetDys)(abdominal obesity, insulin resistance, dyslipidemia, hypertension and systemic inflammation), and are associated with impaired lung function, pulmonary hypertension, and asthma. Silicosis, an occupational lung disease, is caused by inhalation of respirable crystalline silica, which is characterized, in part, by chronic lung inflammation and fibrosis, and significant morbidity and mortality. The purpose of this study is to determine if silica inhalation, and silica inhalation combined with MetDys induced by consumption of a Western diet (WD), affects metabolic disorders as well. For this study, 6-wk-old male F344 rats were fed either a WD [fat 45% Kcal (lard 19.5%, soybean oil 3% by weight), carbohydrate 36.2% Kcal (sucrose 22.2% by weight), protein19% Kcal] or standard rat chow (STD) [fat 6.2% by weight, carbohydrate 45% by weight (grain sources), protein 18.0% by weight, fiber 4% by weight] for 16 wk to initate MetDys, followed by inhalation exposure to respirable crystalline silica (Min-U-Sil 5®, 15 mg/m3) or filtered air 6 h/day, 5 d/week, for 39 d. Endpoints were measured at 0, 4, and 8 wk post-exposure. Animals were maintained on their assigned diets throughout the study. WD increased body mass, abdominal girth, and fat pad weight; silica exposure had no effect on these parameters in STD or WD groups. At 8 wk post-exposure, silica reduced WD-induced increases in serum cholesterol, increased HDL compared to silica alone, and altered alkaline phosphatase, BUN, and BUN/creatine, but had no effect on fasting glucose. Insulin levels were altered by silica in the WD group at 0, 4 but not 8 wk. Leptin levels were decreased by silica exposure in both STD and WD groups. Silica inhalation increased tail arterial pulse frequency (Doppler method) in both STD and WD groups at 8 wk compared to pre-inhalation levels. Silica significantly reduced WD-induced serum inflammatory cytokines INF-γ, CXCL-1, TNF-α, IL-1β, IL-4, IL-5, IL-6, IL-10 and IL-13 compared to the WD air-exposed group at 8 wk post-exposure. Our results indicate that silica inhalation affects WD-induced adipose dysfunction, causing reduction of systemic inflammation and serum leptin in the F344 rat. MetDys-related conditions, including lipid profile, liver, kidney and arterial function, were altered by silica in WD-fed groups, although silica inhalation had no effect on WD-induced weight gain or fat pad mass. In conclusion, silica exposure does not increase the severity of WD-induced obesity but does alter changes in WD-induced organ function, including adipose endocrine function. Reduction of WD-induced inflammation by silica may be a result of a shift in the migration of immune cells to the lung, rather than the adipose tissue, thereby reducing adipose inflammation and subsequent systemic inflammation.