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Cellular stress activates transcription of various genes that mediate stress‐driven proliferation and differentiation in many cells including osteoblasts, endothelial cells, and fibroblasts. In response to mechanical stress, expression of some genes is altered regardless of cell types and that of others in specific cell types. Using the microarray‐based expression data for primary fibroblasts isolated from fetal mouse cornea, skin and tendon, we conducted a model‐based transcription analysis and predicted transcription‐factor binding motifs (TFBMs) responsible for the observed gene alteration. The computational procedure was formulated as a combinatorial optimization problem, and the AntModeler using an ant algorithm was employed to select TFBMs for each of the three fibroblast types. The results indicate that the stress responses are regulated mostly through cell type specific TFBMs together with a limited number of common TFBMs. The predicted role of those TFBMs should be evaluated experimentally.