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Two types of solid lipid nanoparticles (SLNs) were synthesized with loading of (a) gadolinium (Gd) diethylenetriaminepenta acetic acid to construct Gd\u2010SLNs as an MR T1 contrast agent and (b) otcadecylamine\u2010fluorescein\u2010isothiocyanate to construct Gd\u2010fluorescein isothiocyanate (FITC)\u2010SLNs for histologic confirmation of MR findings. Through an in vitro experiment, we first evaluated the size distribution and gadolinium diethylenetriaminepenta acetic acid entrapment efficiency of these SLNs. The SLNs displayed a size distribution of 50\u2013300 nm and a gadolinium diethylenetriaminepenta acetic acid entrapment efficiency of 56%. For in vivo validation, 30 mice were divided into five groups, each of which was administered a transrectal enema using: (i) Gd\u2010SLNs (<jats:italic>n<\/jats:italic> = 6); (ii) Gd\u2010FITC\u2010SLNs (<jats:italic>n<\/jats:italic> = 6); (iii) blank SLNs (<jats:italic>n<\/jats:italic> = 6); (iv) gadolinium diethylenetriaminepenta acetic acid (<jats:italic>n<\/jats:italic> = 6); and (v) water (<jats:italic>n<\/jats:italic> = 6). T1\u2010weighted fluid\u2010attenuated inversion\u2010recovery MRI was then performed on mice after transrectal infusion of Gd\u2010SLNs or Gd\u2010FITC\u2010SLNs, which demonstrated bright enhancement of the colonic walls, with decrease in T1 relaxation time. When Gd\u2010FITC\u2010SLNs were delivered, green fluorescent spots were visualized in both the extracelluar space and the cytoplasm through colonic walls under confocal microscopy and fluorescence microscopy. This study establishes the \u201cproof\u2010of\u2010principle\u201d of a new imaging technique, called \u201cnanoparticle\u2010based MR colonography,\u201d which may provide a useful imaging tool for the diagnosis of colorectal diseases. 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