The construction of the initial structure for preimage attack of MD5 is proposed in this paper. With the help of “divide-and-rule” technique, the successful possibility of the construction is higher than 2-32 . Our construction is based on the MD5 structure, the message modification technique which is improved from Wang’ s. Some related techniques such as the extential form of the signed difference and special role of MSB are applied. According to Sasaki’ s thought, the initial structure separates the one-block MD5 algorithm into two parts and generates two neutral message words corresponding to the two chaining variables. The two message words are independent of each part respectively. Therefore, it can be useful to generate a preimage of MD5 with a complexity of 2123.4 in theory.