The paper by Cinel et al. demonstrates that the inhibition of the effector ROCK with the use of a chemical inhibitor Y27632 improves measures of lung damage from septic rats induced by cecal ligation and puncture (CLP) (9). Inhibiting ROCK reduced edema and cellular infiltrates into the lung presumably by preventing the loss of barrier function in the lung endothelial cells. It also shows the protection from neutrophil activation through the reduction in oxidative products seen in the inhibitor treated rats. This paper demonstrates a target that could be used to treat ALI in humans. Complementary to this finding Riento et al. have identified an endogenous inhibitor of ROCK I called RhoE/Rnd3 which was found to reduce the phosphorylation and activation of the myosin light chain (10). While Ravindraneth et al. identified a partial mechanism for TNF alpha induction of the Rho pathway using a CLP model linking this inflammatory mediator to ALI during sepsis (11). Sepsis produces conditions which produce many activators of the Rho pathway which include thrombin activation, high cytokine production and nitric oxide production (7,12,13). Targeting the Rho pathway could help alleviate the lung injury seen in sepsis in humans. Since the primary treatment for ALI is mechanical ventilation which itself can exacerbate lung injury a treatment that preserves lung function would be beneficial. Better clinical outcomes are associated with preserving lung function or minimizing the time on mechanical ventilation. While the underlying cause of sepsis must be treated the reduction of pulmonary complications induced by sepsis should help improve the outcome of the patient making the development of a therapeutic agent that targets the Rho pathway in lung endothelial cells an important adjunct to sepsis treatment as well as to other causes of ALI. Cinel et al. findings have added further support to targeting this central pathway in endothelial cell barrier function.