In this work, we propose a novel genetic pathway discovery and comparison analysis framework integrating newly generated gene expression microarray data and existing biological pathway information. Starting with the significance analysis of microarray (SAM), a list of differentially expressed genes among groups is obtained. This gene list is then imported to the Ingenuity Pathway Analysis (IPA) to yield potentially relevant biological pathways. Finally, a newly-developed covariate structural equation modeling method is applied to evaluate gene-gene interactions and group difference. We illustrate this novel comparative pathway analysis pipeline using the whole human genome expression profiling data collected from a study of inflammatory bowel diseases (IBD) with 99 subjects from three phenotypic groups: ileal Crohn's disease (CD), ulcerative colitis (UC) and control non-IBD.