Ozone stress induces leaf injuries and yield losses in soybean. To identify the proteins associated with the stress response, ozone tolerant and sensitive cultivars were analyzed by 2D-PAGE. After 11 days of ozone stress unifoliate leaves of tolerant soybean cv. Enrei developed 15% and sensitive cv. Nakasennari developed 52% leaf injury symptoms. Analysis of proteins in the unifoliate leaves identified six proteins in tolerant cv. Enrei and three proteins in sensitive cv. Nakasennari, responded significantly to ozone stress. The significantly responded proteins identified in this study were ATP synthase α-subunit, ATP synthase β-subunit, phosphoglycerate kinase, aldo/ketoreductase, rubiscoactivase and glutamine synthetase. To understand that the differences in response of ATP synthase proteins were ultimately associated with extracellular ATP signaling response, ozone sensitive cv. Nakasennari was treated with 1 mM ATP. Unifoliate leaves of ATP treated plants have significantly reduced injury symptoms (20%) under ozone stress compare to control plants (47%). This confirms that extracellular ATP signaling in ATP synthase dependent manner is playing a pivotal role in inducing ozone stress tolerance and preventing injuries in soybean cultivars.