BACKGROUND High-fat diets (HFD) have recently become a public health concern. We hypothesize that HFD induces exosomes biogenesis in the lung tissue of rat model. RESULTS Sixteen adult male Wistar rats were fed with HFD or a regular chow diet for 3 months. The histopathological changes in lung tissues were measured by hematoxylin and eosin (H&E) staining. Bronchoalveolar lavage (BAL) was performed to assay exosomes by acetylcholinesterase enzyme (AhCE) activity. Real-time PCR (qPCR) was used to evaluate Rab27-b, Alix, and IL-1β expression, while the immunohistochemical examination was performed for CD81 expression in lung tissues. In addition, expression of IL-1β was detected by ELISA. We found pathological alterations in the lung tissue of HFD animals. AhCE activity along with the expression level of Rab27-b, Alix, and IL-1β was increased in HFD animals (p < 0.05). Immunohistochemical staining showed that expression of CD81 was increased in lung tissues of HFD animals compared with the control group (p < 0.05). CONCLUSIONS Hence, HFD induced exosomes biogenesis and histopathological changes with IL-1β expression in rats' lung tissues.