This is a summary of new oxygen isotope data for diatoms from Lake Kotokel sediments, with implications for responses of the lake system and its environment to global change over the past 46 kyr. Fossil diatoms in all samples are free from visible contamination signatures and contain no more than 2.5% Al2O3, which ensures reliable reconstructions. The δ18O values in diatoms vary between +23.7 and +31.2‰ over the record. The results mainly represent diatom assemblages of summer blooming periods, except for the time span between 36 and 32 kyr, when the isotopic signal rather records a shift from summer to spring blooming conditions. Possible water temperature changes only partly explain the changes in the isotopic record. The observed isotopic patterns are produced mainly by isotope changes in lake water in response to variations in air temperature, hydrology, and atmospheric circulation in the region. During Marine Isotope Stage (MIS) 2 (Last Glacial maximum), high δ18Odiatom resulted from rapid evaporation and low fluvial inputs. The high δ18O values of about +29 to +30‰ during the first half of MIS 1 (Holocene interglacial) suggest an increased share of summer rainfalls associated with southern/southeastern air transport. The δ18O decrease to +24‰ during the second half of MIS 1 is due to the overall hemispheric cooling and increased moisture supply to the area by the Atlantic transport. The record of Lake Kotokel sediments provides an example of complex interplay among several climatic controls of δ18Odiatom in the Late Pleistocene and the Holocene.