This study examined the relationship between gingival crevicular fluid (GCF) and serum sclerostin and PGE2 levels and the inflammatory bone resorption associated with chronic apical periodontitis (AP) as well as the correlation between sclerostin regulation and RANKL and MMP-9 levels. Ninety participants were divided into three groups based on PAI scores, as follows: Group 1 (control group, PAI 1-2, n:35); Group 2 (PAI 3-4, n:35); Group 3 (PAI 5 in at least 1 tooth, n:55). Sclerostin, PGE2, RANKL, and MMP-9 levels were measured in the serum and GCF of all participants. GCF sclerostin, RANKL, and PGE2 levels of Group 3 were significantly higher than those of Groups 1 and 2 (75.8 +/- 43.3, 37.0 +/- 6.4 and 42.7 +/- 8.2 ng/mL, p < 0.0001; 319 +/- 167, 244 +/- 41 and 248 +/- 49 ng/L, p = 0.0029; 193 +/- 87, 141 +/- 90 and 137 +/- 79 ng/L, p = 0.0028, respectively for Groups 3, 2, and 1). GCF MMP-9 levels of Group 3 were significantly higher than those of Group 1 (465 +/- 162 and 384 +/- 44 ng/mL, p = 0.0340). Group 3 also had elevated serum sclerostin and PGE-2 levels, but the differences between groups were less pronounced in serum than in GCF (p < 0.05). In the ROC analysis performed for the diagnostic performance of abscess formation in AP, the sensitivity of the GCF sclerostin and GCF PGE2 tests was determined as 65.5% and 72.7%, specificity as 98.6% and 68.6%, and AUC as 0.768 and 0.712, respectively (p < 0.0001). Both GCF sclerostin and PGE-2 independently showed close relationships with PAI-abscess scores used to determine AP severity and they can be used in combination for diagnosing and monitoring AP-related bone resorption.