Objectives: This in situ study was to evaluate the remineralizing effect of a fluoride toothpaste supplemented with nano-sized sodium trimetaphosphate (TMP).Methods: This blind and cross-over study was performed in 4 phases of 3 days each. Twelve subjects used palatal appliances containing four bovine enamel blocks with artificial caries lesions. Volunteers were randomly assigned into the following treatment groups: Placebo (without F and TMP); 1100 ppm F (1100), 1100 supplemented with 3% micrometric TMP (1100 TMP) and with nano-sized TMP (1100 TMPnano). Volunteers were instructed to brush their natural teeth with the palatal appliances in the mouth during 1 min (3 times/day), so that blocks were treated with natural slurries of toothpastes. After each phase, the percentage of surface hardness recovery (%SHR), integrated mineral recovery (IMR) and integrated differential mineral area profile (Delta IMR) in enamel lesions were calculated. F in enamel was also determined. Data were analyzed by ANOVA and Student-Newman-Keuls test.Results: Enamel surface became 20% harder when treated with 1100 TMPnano in comparison with 1100 (p