This study describes a comparison of global proteome expression in small intestinal tissue collected from celiac disease patients at different stages of disease. We have analyzed sections from FFPE biopsy blocks and identified more than 4500 protein without sample pre-fractionation. We have compared protein expression in two sample cohorts that were chosen retrospectively from patients participating in research protocols at our facility. First we compared biopsies from 10 patients collected at the time of diagnoses (untreated CD) with biopsies collected 1 year later following gluten free diet (treated CD). We observed overall good agreement between differential expression of proteins and histological changes that occur in the intestine. We identified biological pathways that are known to operate in the disease lesion. We also observed a strong signal for neutrophil infiltration. By use of a dedicated immunoglobulin variable gene family database we found that differential expression of IGHV5-51 distinguished our untreated from treated CD patients. We also compared protein expression in 4 treated CD patients that developed histological changes in the small intestine in response to a 3 day gluten challenge. Although these patients develop an intestinal lesion resembling the lesion observed in untreated patients, we observed differential expression of proteins involved in acute tissue remodeling that were not seen when we compared UCD to TCD samples. Our study presents a proof-of-concept to demonstrate that analysis of material from FFPE tissue block material can provide a comprehensive overview of many disease processes that occur in the celiac small intestine. Changes in protein expression will reveal information on disease state that may not be observed by histological evaluation