The aim of this study is to improve liposome encapsulation efficiency of water soluble drug ATP-2Na with hydrophobic ion pairing method, and evaluate its effect on tissues energy state in myocardial ischemia mice. Ion pair complex of ATP-2Na with HTAB was prepared first; then the liposomes were prepared by ethanol injection method. The size and zeta potential of ATP-2Na liposome were investigated. Its effect on tissues energy state in myocardium ischemia mice was evaluated by detecting ATP-2Na concentration in tissues and blood after injection in comparison to ATP-2Na solution. The diameters and zeta potential of ATP-2Na liposomes were (144.0 +/- 2.7) nm and (+16.2 +/- 1.6) mV, respectively. The encapsulation efficiency was (85.02 +/- 2.31) %. The in vitro drug release pattern from liposomes matches with Weibull equation. Compared with ATP-2Na solution, ATP-2Na liposome increased the ATP concentration of blood in myocardial ischemic mice very significantly; compared with blank, ATP-2Na liposome increased ATP content of myocardium and liver in myocaridal ischemic mice significantly, but ATP-2Na solution didn't show this effect. ATP-2Na liposome might have an advantage in improving tissue energy state on myocaridal ischemic animals.