Automatic registration in microscopic image sequence is a classical problem, which has not been solved well so far. According to the features of medical microscopic image sequence, the SIFT feature detection method of microscopic image registration is introduced. As large dimension of the traditional SIFT descriptor and its complex algorithm, an improved algorithm of the SIFT is presented, which can reduce the dimension. And a two-way matching algorithm is adopted to eliminate repeated matching points. Random Sampling Consensus algorithm (RANSAC) is applied for removal the wrong matching points to improve the accuracy of matching further. Compared with traditional registration algorithm, the results show that the improved SIFT algorithm has increased both in time-saving and complexity-reducing.