Background: Styrene (ST) has been used for plastic and resin production. It was reported to induce injury of pulmonary tissues. Thymosin β4 (Tβ4), a naturally expressed protein, was reported to have antioxidant, anti-inflammatory, antiapoptotic, and regenerative properties. Aim of study: This study was designed to examine the role of Tβ4 in ameliorating Styrene Oxide (SO)-induced complication on the lung tissues and its potential mechanisms. Material and methods: Forty adult male Wistar albino rats were allocated randomly into 4 groups, 10 rats each. Control group: rats were injected intraperitoneally (i.p.) with 0.5cm physiological saline. Tβ4 group: rats were injected i.p. with 1mg/kg of Tβ4. SO group: rats were injected i.p. with 300 mg/kg of SO. SO+ Tβ4 group: rats were concomitantly injected i.p. with 300 mg/kg of SO and 1mg/kg of Tβ4. All chemicals were given once daily for 28 days. Results: There was a high significant decrease in the body weight, TAO and GSH levels and a significant increase in lung indices, inflammatory markers (TNF-α, IL-1β, and IL-13) and lipid peroxidation marker (MDA) levels in SO group. Also, there was a high significant increase in TGF-β1 and decrease in PGE2 in the SO group. SO also induced marked histopathological changes in lung tissues involving thickened interalveolar septa, collapsed alveoli, and infiltration by inflammatory cells. Also, there were excess collagen fiber depositions, increased number of macrophage cells, and positive α-SMA, CD68 and VEGF immunoreactivity. These results were significantly ameliorated via Tβ4 administration. Conclusion: Tβ4 was effective in preserving the structure and function of the lung after the injury induced by SO.