The invention relates to a high temperature resistant anti-salt isolation solution and a preparation method thereof. The isolation solution comprises 0.85 to 1.80 weight parts of fluid loss additive, 0.43 to 0.90 weight parts of suspension stabilizer, 0.21 to 0.45 weight parts of streaming regulator, 45 to 355 weight parts of density regulator, 100 weight parts of clean water and 0 to 36 weight parts of NaCl. The fluid loss additive is 2-acrylamide-2-methyl propanesulfonic acid or sulfonated-methylbrowncoal, the suspension stabilizer is poly anionic cellulose or xanthan gum, the streaming regulator is sulfonated methyl tannin or sulfomethyl ketoaldehyde resin, and the density regulator is barite powder or iron ore powder. The isolation solution of the invention has strong weighting capability and excellent chemical compatibility of drilling solution, can be prepared into fresh water isolation solution and saline isolation solution, and has high temperature resistant anti-salt property.