The current study aims to investigate the possibility of using solid lipid nanoparticles (SLNs)-enhanced magnetic resonance (MR) colonography to diagnose colorectal cancer. Gd-FITC-SLNs were synthesized by loading gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) and fluorescein isothiocyanate (FITC) simultaneously. Twenty mice received azoxymethane/dextran sulfate sodium (AOM/DSS) to induce adenocarcinoma of the colon and were divided into 4 groups, and 5 in per group. MR colonography were performed at different time periods before and after enema or intravenous injection of Gd-FITC-SLNs or Gd-DTPA. The results demonstrated SNR (signal-to-noise ratio) significantly increased from 1.56- to 1.76-fold within the colorectal tumors after the enema of Gd-FITC-SLNs (p < 0.001). No differences in SNR were observed after the enema of Gd-DTPA (p > 0.05). Besides, SNR increased from 1.54- to 1.72-fold within the colorectal tumors after the intravenous injection of Gd-FITC-SLNs (p < 0.001) while SNR increased from 1.39to 1.57-fold within the colorectal tumors after the injection of Gd-DTPA (p < 0.001). In addition, SNR within colorectal tumors significantly increased ranging from 20th to 140th min, and lasted for about 120 min (p < 0.05) after the enema of Gd-FITC-SLNs and SNR within colorectal tumors also significantly increased ranging from 0th hour to 8th hour, lasted for about 8 hour (p < 0.05) after the injection of Gd-FITC-SLNs. However, after the injection of Gd-DTPA, SNR within colorectal tumors significantly increased only ranging from 0th min to 20th min after administration (p < 0.01). Furthermore, hematoxylin and eosin (H&E) staining revealed that all mice developed adenocarcinoma of the colon. In summary, it is feasible by using Gd-FITC-SLNs in MR colonography to diagnose colorectal cancer. Enema of Gd-FITC-SLNs can provide marked enhancement of colorectal tumors quickly, and safer while intravenous injection of Gd-FITC-SLNs can provide a long-lasting enhancement of colorectal tumors in MR colonography. These findings present a potential clinical application of Gd-FITC-SLNs on MR colonography.