Resistant starch (RS) is a complex carbohydrate that reaches the large intestine and is fermented by the colonic microflora. Two types of novel starches were processed: (1) stearic-acid complexed high-amylose cornstarch (SAC) which contains high resistance and (2) Guat from an inbred corn line with a high resistant starch content and ARXGuat from a hybrid of two corn lines AR (digestible starch) and Guat (resistant starch). The inhibition by SAC on colorectal carcinogenesis was compared with high amylose starch (HA) and normal corn starch (CS), and the study for the same purpose on Guat and ARXGuat starches was compared with AR starch. In all of the studies, starch diets were fed to Azoxymethane (AOM) - induced Fisher 344 rats for 8 weeks with 50-55% of the diet replaced with RS. The cooking method of water-boiling was applied to both studies. A bread-baked method was also applied to the SAC study for the comparison of the cooking methods. In the SAC study, the amount and concentration of Short Chain Fatty Acids (SCFAs) were assessed. Global gene expression was also studied in the colon mucosa of rats fed different diets or injected with AOM/saline by Affymatrix Microarray. Target genes differentially expressed after AOM treatment, or by the feeding of SAC were selected and identified by semi-quantitative real-time polymerase chain reaction analysis (semi-qRT-PCR). In our studies, SAC cooked by either the water-boiling or bread-baking method markedly reduced the Aberrant Crypt Foci (ACF) and Mucin Depleted Foci (MDF) numbers, and an enhanced ACF multiplicity was observed compared with cooked HA or CS within their cooking groups. Aberrand crypt foci numbers were dramatically decreased in the rats fed starches cooked by the bread-baking method compared with that in rats fed starch prepared by the water-boiling method. Increased cecal weights and decreased cecal content pH, as well as increased total SCFAs or individual SCFA (butyrate, acetate) amounts were obtained by the same comparison. Microarray screening identified 3368 induced and 3060 repressed genes by AOM treatment and 544 induced and 859 repressed genes by SAC treatment, among which seven genes were confirmed by semi-qRT-PCR. In the Guat and ARXGuat study, Guat was found to cause a slight but significant increase in the ACF multiplicity, but no significant differences were found in total number of ACF, MDF or AC in rats fed either Guat or ARXGuat, relative to those fed AR. Collectively, the studies suggested the inhibitory effect of novel RS SAC on colonic preneoplastic lesions after the starches were cooked. It also revealed that the rats fed starch diets prepared by bread-baked cooking method had decreased preneoplastic lesion numbers compared with those fed water-boiled starch diets.