The cDNA microarray image provides useful information about thousands of gene expressions simultaneously. This information is used by bioinformatics researchers for diagnosis of different diseases and drug designs. Microarray image spot segmentation using an improved fuzzy clustering algorithm is proposed in this article. The proposed Possibilistic Reformed Fuzzy Local Information C Means (PRFLICM) algorithm is a variant of Possibilistic Fuzzy Local Information C Means (PFLICM) algorithm. The parameters used for testing the proposed algorithm include segmentation matching factor (SMF), probability of error (p e ), discrepancy distance (D), normalized mean square error and sum of square distance (SSD). The performance of the algorithm is validated with a set of simulated cDNA microarray images with known gene expression values. From the results of SMF, the proposed PRFLICM shows an improvement of 0.4% and 0.1% for high noise and low noise microarray images respectively when compared to PFLICM algorithm. The proposed algorithm is applied to yeast microarray database (YMD) and is used to find the yeast cell life cycle generated genes. The results show that the proposed algorithm has identified 101 cell life cycle regulated genes out of 104 such genes published in the YMD database.Keywords: Fuzzy clustering, gene expression, image processing, microarray.cDNA microarray technology helps molecular biologists to measure simultaneously the activity of thousands of biomolecules in the cell under different experimental conditions [1][2][3] . This powerful tool in biotechnology has been utilized in many biomedical applications such as cancer research, infectious disease diagnosis, toxicology research, pharmacology research and agricultural development. Spots foreground (FG) from microarray image are segmented from the background (BG) to compute gene expression (GE). The stages involved in microarray image processing are gridding, segmentation, information extraction and GE computation.These operations are used to find the accurate location of each spot, separate each spot FG from BG and compute GE value. The log to the base 2 value of the ratio of mean or median red and green plane intensities of each spot FG is the GE value.Zacharia and Maroulis 4 proposed a 3D model for microarray spot segmentation where a 3D model was used to represent spot in a 3D space. The 3D space was optimized using genetic algorithm.Athanasiadis et al. 5,6 proposed two algorithms, fuzzy gaussian mixture model (FGMM) and wavelet markov random field (WMRF) model for segmenting microarray spots. The methods were applied on both simulated and real microarray images.Uslan et al. 7 used two clustering methods, Fuzzy CMeans (FCM) and K-means algorithms for segmentation of microarray image spots. Results showed that FCM could segment spots more accurately than K-means algorithm, but the segmentation accuracy of FCM was poor in medium and high noise spots.The Genetic Algorithm based Fuzzy C Means (GAFCM) 8 method was applied to cDNA microarray images for s...