Rats exposed to the quaternary herbicide paraquat (PQ) exhibit oxidative stress and lung injury. In the present study, we investigated the effect of multiple exposures to PQ on aerobic performance during progressive exercise on a treadmill in rats. PQ was dissolved in saline (SAL) (10 mg/ml) and administered intraperitoneally 7 mg/kg body wt to Wistar rats (n = 5) once a week for one month. Control rats received SAL (0.7 ml/kg body wt., intraperitoneally, n = 5) over the same time period. The animals were submitted to aerobic evaluation on a treadmill using a progressive protocol until fatigue prior to the administration of the first dose of PQ or SAL and repeated at 1 week and 40 days following the last dose of the herbicide. Twenty-four hours after the last performance tests, the animals were sacrificed, lungs removed and divided in two groups: PQ and SAL for histopathological analysis. The animals exposed to PQ exhibited decrease in aerobic performance and mechanical efficiency (ME) as well as increase in oxygen consumption during exercise in comparison to the controls forty days after the last dose of PQ. Lung histologic changes included atelectasis, interstitial edema, and inflammation cells in PQ group. The collagen system fibers, fraction area of alveolar collapse and influx of polymorphonuclear (PMN) cells in lung parenchyma were higher in PQ compared to SAL. In conclusion, multiple exposures to PQ induce pulmonary fibrosis, reduce the aerobic performance and mechanical efficiency and increase the metabolic cost of exercise in rats.